Epithelial ovarian cancer is one of the most common gynecologic malignancies and the fifth most frequent cause of cancer death in women with an estimated incidence of about 15,000 in 2006 in the US alone. Most patients present with advanced disease and the mortality rate is approximately 65% of the incidence rate. Debulking surgery and platinum-based combination chemotherapy (including taxanes) are current treatment modalities; however the majority of patients with relapsed epithelial ovarian cancer eventually succumb to the disease. Thus, there is a need for novel treatment modalities in ovarian cancer, including targeted therapies such as immunotherapy with monoclonal antibodies or cancer vaccine-based approaches.
Monoclonal antibody MX35 was generated from mice immunized with a cocktail of human ovarian carcinoma cells prepared from four different surgical specimens. Reactivity by immunohistochemistry with cryostat sections of a panel of frozen human tissues was used as the major hybridoma selection criteria (1). Mab MX35 showed homogeneous reactivity with approximately 90% of human ovarian epithelial cancers and a limited number of normal tissues. Subsequently, the localization and biodistribution of radiolabeled murine antibody was studied in patients with ovarian carcinoma in phase I clinical trials. Intact MX35 antibody targeted well to tumors in patients with ovarian cancer (2) and F(ab′)2 of MX35 was shown to localize to micrometastatic ovarian carcinoma deposits within the peritoneal cavity (3). In preparation for the use of the antibody for radioimmunotherapy, e.g. as a targeted carrier of radionuclides in patients with ovarian carcinoma, the murine antibody and its fragments are currently being investigated in preclinical models (4, 5) and in a phase I clinical trial in patients with ovarian cancer as carrier of the alpha-particle-emitting nuclide astatine-211 (6).
Despite the use of mAb MX35 in clinical trials the detailed molecular nature of the antigen recognized by mAb MX35 has not yet been identified. Initial immunochemical characterization has described the MX35 antigen as a 95 kDa cell surface glycoprotein with the antigenic epitope stabilized by disulfide bonds (7).
The identification and characterization of the mAb MX35 antigen and epitope would provide a target for immunotherapy of cancer with monoclonal antibodies and for other cancer treatment modalities, including improved and directed cancer therapeutic compounds, and a recognized marker for diagnostic and monitoring purposes.
The citation of references herein shall not be construed as an admission that such is prior art to the present invention.